The present invention is related to the drug for the treatment of gastric disease especially to a Chinese drug composition for the treatment of peptic ulcer and preparation thereof.
Peptic ulcer is a common, frequently-occurring disease with high incidence. The aim of the therapy of peptic ulcer is to eliminate symptoms, promote healing, and to prevent relapse and complications. At present the medicines used in the treatment of peptic ulcer still do not meet the therapeutical demands. The drugs utilizing in the treatment of peptic ulcer at present are all exiting the defects of expensive price, obvious side effects, and high relapse.
In Chinese medicine, peptic ulcer related to the categories of xe2x80x9cepigastric painxe2x80x9d, xe2x80x9cstomachache caused by the dominant liver-energyxe2x80x9d and so on. The mechanism of the disease mostly is concerned with the deficiency of qi in the spleen and stomach, or the stagnation of vital energy caused by cold-evil, or the obstruction of the stomach caused by damp-heat, or the internal stagnation of the blood and so on. The hindrance of functional activities of qi yields the pain, and the stagnation of qi leads to blood stasis, or prolonged diseases involves the collateral, the prolonged blood stasis in the interior changes into heat then the flesh was rotted and the muscles was injured and the ulcer was formed. xe2x80x9cNeiJing SuWen: JuTongLun (Plain Question of Canon of Internal Medicine: On the Pain)xe2x80x9d: xe2x80x9cthe cold-evil accumulated between the stomach and intestinal under the half-superficies and half-interior position so that pain was formed due to the blood failed to circulate and the small collateral was blockedxe2x80x9d, xe2x80x9cthe cold-evil accumulated in the stomach and intestinal adversely evolved from upside resulted in pain and vomitxe2x80x9d. In clinics, many cases were categorized in cold-evil accumulating in stomach, stagnation of qi leads to blood stasis, Ye Tian-shi of Qing dynasty gave a brilliant exposition on the therapeutical method: xe2x80x9cWhat is the essential of (stomach disease)! The beginning of the disease mentioned above is occurred at the channel then goes into the collateral as a result of prolonged pain, channel is the principal pathogeny and collateral controls the blood, therefore the treatment of qi and blood is abundantly clearxe2x80x9d. (xe2x80x9cLin Zheng Zhi Nan Yi An, Wei Wan Tong (Medical Record Guides of clinical Symptoms Epigastric pain)xe2x80x9d). Li Dong-huan pointed out in xe2x80x9cNei Wei Shang Pian Huo Lun, Fei Shi Pi Wei Xu Fang (On the recognition of the Nature of internal and traumatic injuries, Formula of the deficiency of Spleen and Stomach due to Lung)xe2x80x9d. xe2x80x9cFire has been exhausted and can not be transported and transformed, in addition of the invasion by cold-evil, all of this accumulated as fullness pain. Dispelled it with pungent hot medicine and associated with sweet-bitter ones to use bland flavor drug for clearing up then qi become gentle and stomach become harmony, as a result the pain would be relievedxe2x80x9d.
At present, using the drug prepared from two kinds of Chinese medicine indicated as follow for the treatment of peptic ulcer still has not been reported. This two kinds of medicine are:
Chenopodium ambrosioides (cf. Du Yao Ben Cao (poison Herbs) ed. by Yang Lun-liang pp 925-927. China Chinese Medicine Publish House, Dec. 1993): Chenopodium ambrosioides is the total herb with the ear of fruit of the plant of Chenopodiaceae chenopodium ambrosioides L. The essential oil (oil of Chenopodium ambrosiodes) contained in the total herb is 0.4-1% composing mainly of Ascaridole, p-Cymene, and other terpeniod such as aritasone, limonese etc. possesses the activities of dispelling wind-evil, killing germs, inducing menstruation and relieving pain.
Adina pilulifera (cf. Zhong Hua Yao Hai (Chinese Medicine Dictionary) ed. by Ran Xian-de p426, Harbin Publish House, Aug. 1993); It is a plant of Rubiaceae, the scientific name is Adina pilulifera (Lam Franch). Its leaves contain the admixture of acidic saponin which gave quinovic acid and acetate thereof aftwr hydrolysis, it also contains beta-sitosterol, and its stern contains quinovic acid, beta-sitosterol and the admixture of saponin which yields quinovic acid, betulic acid and cinchoninic acid after hydrolisis. The fraction of saccharide contains mainly glucuronate. It exhibits the effect of clearing away heat and dampness, removing blood stasis and relieving pain, arresting blood and promoting the regeneration of tissues and so on.
The object of the invention is to overcome the deficiency of the prior art and to provide a Chinese drug composition comprising mainly of the active components of chenopodium ambrosioides and adina pilulifera for the treatment of peptic ulcer.
The another object of the present invention is to provide a method for preparing said Chinese drug composition.
The still another object of the present invention is to provide a capsule preparation comprising said Chinese drug composition.
The further object of the present invention is to provide a use of said Chinese drug composition in the preparation of drug for the treatment of peptic ulcer.
The present invention provides a Chinese drug composition for the treatment of peptic ulcer which comprises the oil of Chenopodium abrosioides and the oil of Adina pilulifera, in a ratio of oil of Chenopodium ambrosiodes: oil of Adina pilulifera being 18-70:0.5-5 (by weight).
The Chinese drug composition of this invention was prepared according to the following procedure, that is:
Chenopodium ambrosioidesand Adina pilulifera (50-70:30-50 by weight) were steam distilled for extracting the essential oil, and collecting the oil obtained.
The preparation containing the Chinese drug composition of this invention can be administered with any oral preparations preferable is capsules, its preparative method may be the regular method known in the existing art.
The Chinese drug composition of present invention possesses good therapeutic effect on peptic ulcer and is provided with significant inhibitory action to pyloric spirillum.
The Chinese drug composition of this invention is the active components extracted from Chenopodium ambrosioides(Chenopodiaceae) and Adina pilulifera(Rubiaceae) which were the essential oils obtained by steam distillation of Chenopodium ambrosioides and Adina pilulifera in a ratio of 50-70:30-50 by weight. The essential oil obtained was a mixture comprising the oil of Chenopodium ambrosioides and oil of Adina pilulifera oil of Chenopodium ambrosioides: oil of Adina pilulifera therein is 18-70:0.5-5 (by weight).
The source of the medicines of this invention is spread in everywhere, and the price of the medicines is cheap. The preparative procedure is simple and easy to conduct which is advantageous to decrease the product cost.
The results of animal tests indicated that the Chinese drug composition of present invention possesses good protective effect to the ulcer of stress, pyloric ligation, acetic acid burn, and Reserpine, Indomethacin and Histamine induced peptic ulcer (details are shown in experiments 1-1 to 1-6 thereinafter).
The generally accepted mechanism of peptic ulcer was the xe2x80x9cbalance theoryxe2x80x9d suggested by Shay which meant that the defending factors and the attacking factors were in a state of imbalance. Anti-ulcer agents showed the therapeutic effect through promoting the defending factors or by retarding the attacking factors.
The stress ulcer is generally considered as an acute ulcer caused by the disorder of central nerve system and automatic nerve system function and the disorder of gastrointestinal peristalsis and secretion.
The mechanism of pyloric ligation ulcer is considered to be the result of the accumulation of acid and pepsin. The ulcer induced by Reserpine is related to the stimulation of vagus and the increase of gastric secretion.
The increased secretion of gastric juice with high acidity induced by Histamine is probably an important factor of ulcer occurrence. The medicine of the present invention possesses significant inhibition to the four kinds of acute gastric ulcer mentioned thereinbefore and associated with the effects of decreasing secretion and inhibition of the gastric acid and pepsin activity. All of these indicated that retarding the attacking factors is one of its anti-ulcer mechanism.
Indomethacin decreases the amount of prostaglandin which possesses potent cell protection effect in gastric mucosa by inhibiting cyclooxygenase in the mucosa and interfering biosynthesis of prostaglandin, thus affected the mucosal epitheliosis, mucus formation and the blood supply in mucosa resulted in retarding the defending ability and leaded to the occurrence of ulcer.
The medicine of this invention can effectively inhibit the ulcer induced by Indomethacin. The determination of the Alcian blue absorption by the binding mucus of stomach wall indicated that the another mechanism of the medicine is to promote the synthesis of gastric mucus and enhance the defending ability of gastric mucosa.
Ulcer caused by acetic acid is a model of chronic ulcer. Its characterization is similar to the human peptic ulcer, with prolonged healing duration, and is a kind of chronic obstinate ulcer. The medicine of this invention can significantly decrease the ulcer volume burned by acetic acid indicating that it has the effect of promoting the healing.
Pyloric spirillum is closely related with chronic gastritis, gastric and duodenal ulcer, and the relapse of the ulcer hence was increasingly taken seriously. The inhibitory test in vitro to pyloric spirillum showed that the medicine of the present invention possesses drastic inhibitory activity. MIC of this medicine is 0.024-0.048 mg/ml. According to the dose used in clinical trial (each time 100 mg) concentration of the medicine in the gastric juice is far exceeded MIC. This is the another therapeutic mechanism of the medicine of the present invention for the treatment of peptic ulcer.
In addition, the medicine of the present invention shows drastic inhibitory activity to gastrointestinal peristalsis, and antagonizes Ach, BaCl2, His against agonization on gut. The antispastic action on gastrointestina smooth muscle can relieve pain caused by the ulceration of upper digestive tract.
The results of clinical application to 633 patients suffering peptic ulcer showed that the total effective rate is 95.26% and the cure rate is 80.88%.
The therapeutic effect of the medicine of this invention is better than that of single Chinese drug. The water decocted preparation of Chenopodium ambrosioides and Adina pilulifera which was prescribed according to the ratio thereinbefore in still efficacious. The effective rate of 960 clinical cases is 75% and the cure rate is 62%.
It is obvious that the medicine of this invention possesses significant therapeutic effect to peptic ulcer.
Chenopodium ambrosioides comprised in the medicine of present invention possesses definite toxicity. The results of its acute toxic test is:
LD50 (ig)=93.1 mg/kg 
LD95=93.1xc2x118.5 mg/kg (74.5xe2x88x92111.5 mg/kg) 
The results of long term toxic test is identical with that of Chenopodium ambrosioides. The employed dose of the drug of this invention should be less than the toxic dose.
The dose of the medicine of present invention used in clinic is generally about 300 mg/day, preferably is about 240 mg/day.
Excepting the preparation of capsule described in this text, the drug of present invention can be prepared into any suitable dosage forms, such as capsules. Owing to the specific odor of the essential oils, preparation of capsule is preferred. Its preparative method is the regular procedure known in the art, the preferable method is: vegetable oil was added to the extracted essential oil for dilution to prepare the material oil. The vegetable oils used for dilution are pharmaceutically acceptable, for example, peanut oil rapeseed oil, and the purified vegetable oils, such as to remove the solid fat at about 0xc2x0 C. is more preferred. Medical gelatin and appropriate amount of medical glycerol were dissolved in distilled water and filtrated to give the gelatin solution. Material oil and gelatin oil were put into the capsule-making-machine and were dropped into capsules. After setting, drying, washing, sterilizing, sorting out, and packing of the prepared capsules the capsules of the drug of this invention were obtained.
The drug of present invention was further described through the following examples and experiments.